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Fig. 6 | BMC Systems Biology

Fig. 6

From: Differentiation resistance through altered retinoblastoma protein function in acute lymphoblastic leukemia: in silico modeling of the deregulations in the G1/S restriction point pathway

Fig. 6

Simulation results of the newly proposed model after estimating its parameters for the mean case. (a) Hypo-phosphorylated retinoblastoma protein (hypo-pRb, purple) although rapidly formatted at the start of the G1-phase, maintains significant levels only for a limited period of time. (b) Hyper-phosphorylated forms of retinoblastoma protein (hyper-pRb all forms, dark yellow) rapidly dominate the total levels of the protein in contrast with the un-phosphorylated form (pRb, grey) which is quickly consumed. (c) Pseudo-hyper-phosphorylated retinoblastoma protein (pseudo-hyper-pRb, dark green) is directly formulated from the very first hours of the G1-phase and exclusively represents the hyper-phosphorylated forms of the retinoblastoma protein until the Modifier Activation time point, after which hyper-phosphorylated retinoblastoma (hyper-pRb, light purple) prevails. (d) Significant free E2F levels (E2F, green) are appointed only after the Modifier Activation. However, adequate levels of E2F are bound to E2F inhibiting pRb forms (orange) for a substantial time interval. (e) Cyclin A levels behavior (red) is consistent with the criteria set, showing decreasing or steady trends for the first hours of the simulation and increasing ones till its end, reaching the G1/S Transition threshold in 5200‚ÄČmin. (f) Cyclin D (light blue) shows insignificant variation in its levels for the entire time course of the simulation

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